Comparison of the effects of vasopressin and norepinephrine on organ perfusion during septic shock in streptozotocin-induced diabetic rats

Comparison of the effects of vasopressin and norepinephrine on organ perfusion during septic shock in streptozotocin-induced diabetic rats
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DOI:
10.1007/s00540-010-0934-1
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发表时间:
2010-04
影响因子:
2.8
通讯作者:
H. Hinohara;Y. Kadoi;Aya Tokue;S. Saito;C. Kawauchi;A. Mizutani
H. Hinohara;Y. Kadoi;Aya Tokue;S. Saito;C. Kawauchi;A. Mizutani
中科院分区:
医学4区
文献类型:
--
作者:
H. Hinohara;Y. Kadoi;Aya Tokue;S. Saito;C. Kawauchi;A. Mizutani

文献摘要

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目的本研究的目的是比较去甲肾上腺素(NE)和加压素对链脲佐菌素诱导的糖尿病大鼠内毒素休克时全身血流动力学、肾和肠系膜动脉血流、炎症反应和诱导型一氧化氮合酶(iNOS)活性的影响。方法本研究设计包括三组实验:(1)测量全身血流动力学以及肠系膜和肾动脉血流的变化; (2)生化变量的测量; (3)肠系膜动脉中iNOS活性的测量。在治疗前和治疗后 1、2 和 3 小时评估全身血流动力学、局部动脉血流变化和生化变量。结果加压素(而非 NE)可以防止主动脉血流减少,但不能恢复肠系膜动脉血流。此外,加压素可以部分恢复糖尿病大鼠的肾动脉血流量。糖尿病大鼠静脉注射 LPS 后,血浆亚硝酸盐水平和肠系膜动脉 iNOS 活性升高。在糖尿病大鼠中,内毒素引起的肠系膜动脉血流减少可通过加压素和非选择性 NOS 抑制剂 NG-硝基-L-精氨酸甲酯 (L-NAME) 部分恢复。此外,l-NAME 还可防止血浆亚硝酸盐水平和肠系膜动脉 iNOS 活性增加。相比之下,在糖尿病大鼠中,内毒素引起的肾动脉血流量减少可被加压素和l-NAME部分恢复,但不能被NE部分恢复。 结论 在链脲佐菌素诱导的糖尿病大鼠败血性休克期间,一氧化氮可能是导致肠系膜和肾动脉对加压素敏感性降低的一个可能因素。
PurposeThe purpose of this study was to compare the effects of norepinephrine (NE) and vasopressin on systemic hemodynamics, renal and mesenteric artery blood flow, inflammatory response and inducible nitric oxide synthase (iNOS) activity during endotoxin shock in streptozotocin-induced diabetic rats.MethodsThe study was designed to include three sets of experiments: (1) measurement of changes in systemic hemodynamics and mesenteric and renal artery blood flow; (2) measurement of biochemical variables; and (3) measurement of iNOS activity in the mesenteric artery. Systemic hemodynamics, regional artery blood flow changes and biochemical variables were assessed before treatment and 1, 2 and 3 h after treatment.ResultsVasopressin, but not NE, prevented the decreases in aortic blood flow, but did not restore mesenteric artery blood flow. In addition, vasopressin partially restored renal artery blood flow in diabetic rats. Plasma nitrite levels and iNOS activity in the mesenteric artery were elevated after intravenous LPS in diabetic rats. Endotoxin-induced decreases in mesenteric arterial blood flow were partially restored by vasopressin with nonselective NOS inhibitor,NG-nitro-l-arginine methyl ester (l-NAME), in diabetic rats. Moreover,l-NAME prevented increases in plasma nitrite levels and iNOS activity in the mesenteric artery. In contrast, endotoxin-induced decreases in renal arterial blood flow were partially restored by vasopressin withl-NAME, but not by NE in diabetic rats.ConclusionsNitric oxide may be one possible contributor to reduced sensitivity of the mesenteric and renal arteries to vasopressin during septic shock in streptozotocin-induced diabetic rats.